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Biomedical subjects

D J Reen

Publications and source records attributed to D J Reen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Antibody response of restricted isotype to heat shock proteins in juvenile chronic arthritis.

Synovial fluid and peripheral blood mononuclear cells from juvenile chronic arthritis (JCA) patients have previously been shown to exhibit substantial proliferative responses to both human and mycobacterial heat shock protein (hsp) 65. We investigated the nature of the antibody response to mycobacterial and E. coli hsp 65 and human and E. coli hsp 70 in 56 JCA patients using an ELISA. Elevated levels of antibodies to both human and E. coli hsp 70 were demonstrated. With hsp 65, raised levels of antibodies to the mycobacterial but not the E. coli protein were detected. Overall, 48% of patient serum samples contained antibodies of at least one isotype to mycobacterial hsp 65. These antibodies were predominantly of IgG and IgM isotype, a finding in contrast to adult rheumatoid arthritis, where IgA and IgG isotypes are most often detected.

Adolescent↗
PubMed1992

Early induction of IL-6 in infants undergoing major abdominal surgery.

Cytokines are immunoregulatory molecules that are important mediators of the host response to stress and infection. Infants and children undergoing major surgery are particularly at risk of developing sepsis and have altered metabolic responses to surgical stress compared to adults. We have investigated the temporal sequence of cytokine responses in six infants (mean age, 11 +/- 7.5 months) undergoing pull-through operation for Hirschsprung's disease and correlated them with hemodynamic and biochemical parameters. Tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA preoperatively, intraoperatively (hourly), and 24 and 48 hours postoperatively. IL-6 levels increased significantly in all cases within 2 hours of commencement of the operation (P less than .01) and were maximal 24 hours postoperatively. No significant changes in IL-1 beta levels (mean range, 70 to 110 pg/mL) were seen in these patients. TNF levels were undetectable (less than 20 pg/mL) throughout the study. Cortisol levels were increased in all patients during operation. Serum C-reactive protein levels were first detected 24 hours postoperatively and continued to increase 48 hours postoperatively. Hemodynamically, heart rate increased during the first 3 hours of operation and correlated with increase in IL-6 levels. Blood pressure and temperature changes did not correlate with cytokine levels. This study identifies IL-6 as the earliest detectable cytokine response associated with major surgery in infants. It also suggests that IL-6 can be unregulated, independently of other cytokines, in response to surgical stress.

C-Reactive Protein↗
PubMed1992

Characterization of antibody-mediated inhibition of Pseudomonas aeruginosa adhesion to epithelial cells.

An enzyme-linked immunosorbent assay system was developed and used to study adhesion of Pseudomonas aeruginosa to human epithelial cells and the abilities of specific antibodies to inhibit this process. Human buccal epithelial cells coated onto microtiter plates were incubated with P. aeruginosa suspensions, and adherent bacteria were detected by using anti-P. aeruginosa serum and a horseradish peroxidase-conjugated secondary antiserum. Adhesion, quantitated as an increase in A405, varied linearly with increasing numbers of bacterial CFU added per well in the range of 10(5) to 10(8) CFU per well. Adhesion of P. aeruginosa increased following trypsinization of buccal epithelial cells. Preincubation of bacteria with monoclonal antibodies directed against P. aeruginosa outer membrane protein H2 inhibited adhesion with all eight of the isolates tested. Preincubation of P. aeruginosa with sera from infected cystic fibrosis patients also resulted in inhibition of adhesion in the enzyme-linked immunosorbent assay system. This inhibitory activity was shown to be due to two factors: P. aeruginosa-specific immunoglobulin G and a non-immunoglobulin G serum component. These data support the hypothesis that bacterial components other than pili are involved in adhesion and suggest that anti-P. aeruginosa antibodies may be of use in preventing adhesion and subsequent colonization with P. aeruginosa.

Animals↗
PubMed1992

Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung's disease.

Enterocolitis remains an important cause of morbidity and mortality in Hirschsprung's disease. The aetiology of enterocolitis is uncertain-ischaemic and bacterial causes and recently, rotavirus infections, have been suggested. Bowel tissue from 12 patients with Hirschsprung's disease who underwent Swenson's operation (five of whom had clinical evidence of enterocolitis) and colon from six controls subjects were examined to investigate possible immunopathological mechanisms associated with the disease. IgA, IgM, and J chain (but not IgG) containing plasma cells were significantly increased in the lamina propria along the entire length of resected bowel in enterocolitis patients, compared with non-enterocolitis patients and controls (p less than 0.01). Luminal secretory component staining of the anganglionic segment of colon from enterocolitis patients was considerably reduced. Lamina propria CD68 positive monocyte/macrophages and CD45RO positive leukocytes were increased in enterocolitis patients compared with non-enterocolitis patients (p less than 0.01). CD57 positive natural killer (NK) cells showed a unique distribution pattern compared with other cell types. Patients with enterocolitis showed a significant increase in CD57 positive NK cells in the lamina propria of ganglionic bowel only (p less than 0.05). NK cell values in ganglionic bowel of non-enterocolitis patients and in aganglionic bowel in all patients were similar to controls. The diversity of altered local immune response seen in this study may reflect a multifactorial microbial aetiology in enterocolitis associated with Hirschsprung's disease.

Antigens, CD↗
PubMed1989

Analysis of complement factor B activation by PAGE-immunoblotting.

Initiation of complement activation via the alternative pathway results in cleavage of Factor B into two fragments Ba and Bb. Employing PAGE and immunoblotting analysis we have demonstrated Ba and Bb activation fragments following in vitro and in vivo activation in a range of biological fluids including cerebrospinal fluid and synovial fluid. Quantitative linearity was obtained over the range 5-20 micrograms/ml of Factor B and its fragments in body fluids. Using Davis-PAGE a previously unrecognised triple component heterogeneity of the Ba fragment was observed. This study demonstrates that immunoblotting may be used as a sensitive and quantitative tool for the detection and characterisation of the individual cleavage products of Factor B in complex biological fluids without prior purification.

Cardiopulmonary Bypass↗
PubMed1988

Inflammatory response in enterocolitis in the piebald lethal mouse model of Hirschsprung's disease.

Mucosal immune defense responses in two clinical forms of enterocolitis complicating congenital megacolon in the piebald lethal mouse model of Hirschsprung's disease were investigated. Significant histological and immunocytochemical differences were seen in the ganglionic segment of colon between piebald mice with early clinical onset of acute illness and piebald mice with late onset enterocolitis. The number of IgA-containing plasma cells infiltrating the lamina propria of the gut in the former group were significantly increased (p less than 0.001) compared to the latter group of mice and healthy controls. This study suggests that the two forms of enterocolitis complicating congenital megacolon in piebald mice have different etiologies.

Animals↗
PubMed1987

Immunohistochemical characterization of abnormal innervation of colon in Hirschsprung's disease using D7 monoclonal antibody.

Innervation patterns in normal and aganglionic colon were studied using a panel of antineuronal cell antibodies. One antibody, D7, which recognizes a subset of neuronal cells of the peripheral and central nervous system reacted strongly with nerve fibers in the circular muscle of the normal colon. Immunohistochemical scanning of the entire resected specimen of colon from three children with Hirschsprung's disease demonstrated large numbers of D7 immunoreactive nerve fibers in the circular muscle of the ganglionic colon, few fibers in the transitional zone, and no immunoreactive fibers in the aganglionic segment of bowel. While the absence of D7 immunoreactive fibers paralleled the absence of myenteric ganglion cells in the aganglionic segment, a critical region of colon was identified wherein D7 reactive fibers were evident ahead of the appearance of ganglion cells. These findings indicate that the fundamental pathology in Hirschsprung's disease is not only the absence of ganglion cells of the myenteric and submucuous plexuses but also the absence of D7 immunoreactive fibers in the circular muscle of the colon.

Antibodies, Monoclonal↗
PubMed1985

Effect of methotrexate on the immune response in children with acute lymphatic leukaemia.

Lymphocyte count, lymphocyte subpopulations identified by monoclonal antibodies and mitogen stimulation assays with phytohaemagglutinin, concanavalin A, pokeweed mitogen and staphylococcal protein A, were used to quantitate the effect of methotrexate on the immune response in children with acute lymphatic leukaemia on maintenance therapy. Methotrexate exerted a profound but apparently short-term effect on these parameters as it is prescribed in current maintenance schedules for childhood acute lymphatic leukaemia. A significant drop in lymphocyte count, affecting all subpopulations, was observed 4 h after oral or intramuscular administration of methotrexate which had reverted to pre-methotrexate values one week after the drug was given. Lymphocyte function was markedly affected, with a major decrease in mitogen responsiveness 1 h after methotrexate and a reversion to pre-methotrexate values by 48 h. A selectivity of suppressor T cells to methotrexate is proposed as being responsible for early recovery. Scheduling of methotrexate in current maintenance programmes would therefore appear to allow adequate time for recovery of immunoresponsiveness between doses.

Age Factors↗
PubMed1985

Identification of rectal ganglion cells using monoclonal antibodies.

A monoclonal antibody has been developed that reacts specifically with ganglion cells of the myenteric and submucous plexuses of the gastrointestinal tract. This antibody also recognizes an axonal antigen that is distributed throughout the circular muscle of normal colon and rectum. Aganglionic segments of colon and rectum from patients with Hirschsprung's disease showed no specific antibody binding using a fluorescent labelled assay. The use of monoclonal antibodies should provide further insights into the pathophysiology of Hirschsprung's disease and allied disorders.

Antibodies, Monoclonal↗
PubMed1985

Augmentation of pokeweed mitogen-induced immunoglobulin production by cord T-cell supernatants.

Adult mononuclear cells were stimulated with pokeweed mitogen (PWM) in the presence of supernatants from cord T cells which had been previously stimulated with PWM for 24 h. Increased IgM, IgG and IgA production, as measured by ELISA, was observed with the addition of increasing concentrations of cord T-cell supernatants. The most significant increase in immunoglobulin production was observed with IgM (p less than 0.001). Cord T lymphocytes appear to be capable of producing soluble helper factors which augment immunoglobulin production by adult lymphocytes.

Adult↗
PubMed1985

The effect of methotrexate on in vitro immunoglobulin production.

The effect of Methotrexate (MTX) on pokeweed mitogen (PWM) induced immunoglobulin (Ig) production in vitro was studied over a range of 10(-4) - 10(-12)M MTX, using an enzyme-linked-immunosorbent assay (ELISA). MTX, at a concentration of 5 X 10(-9)M profoundly decreased all classes of Ig production, IgM greater than IgG greater than IgA. Plasma cell numbers, identified using polyclonal antihuman immunoglobulin, demonstrated a similar sensitivity to MTX. There was a paradoxical increase in IgM and IgG production at 5 X 10(-11)M MTX. Clinical implications of these findings are discussed.

Dose-Response Relationship, Drug↗
PubMed1984

Immunosuppressive effects of anesthesia and surgery in the newborn: I short-term effects.

We examined short-term effects of anesthesia and surgery on the lymphocyte response of neonates and older children to a range of mitogens using a whole blood mitogen stimulation assay. Following induction of anesthesia, both neonates and older children demonstrated significantly decreased lymphocyte transformation to phytohaemagglutinin (PHA; P less than 0.005) and Con A (P less than 0.025) compared with preanesthetic values. Immediately, postsurgery, older children recovered fully their responsiveness to both PHA and Con A, while there was significant depression in their responsiveness to PWM (P less than 0.005) and SPA (P less than 0.05). In contrast, neonatal responsiveness to all mitogens was significantly reduced (P less than 0.005) immediately after surgery compared to preoperative values. At 24-hour postsurgery, neonatal responsiveness to PHA had returned to preoperative levels but Con A, PWM, and SPA responses continued to decline (P less than 0.005). These results suggest that the newborn is particularly susceptible to the immunosuppressive effects of anesthesia and surgery.

Anesthesia, General↗
PubMed1984

Atopy, immunological changes, and respiratory function in bronchiectasis.

Cystic fibrosis has been reported to be associated with an increased prevalence of atopy and reversible airways obstruction. To determine whether such features can also result from other chronic suppurative lung infections, we studied 23 patients with proved bronchiectasis, and 23 age and sex matched normal controls. A personal or family history of atopy was reported with equal frequency in the two groups. Although the groups displayed a similar prevalence of positive immediate hypersensitivity skinprick test responses, the positive patients reacted to more antigens (p less than 0.05) and had larger weal diameters (p less than 0.01) than the positive controls. Other indices, such as blood eosinophil counts and serum IgE, did not differ significantly. Serum concentrations of immunoglobulins G, A, and M and of the four IgG subclasses tended to be higher in patients than controls, but only in the case of IgA (p less than 0.01) was this difference significant. No case of IgG subclass deficiency was noted. The patients displayed significant airflow obstruction, the mean basal one second forced expiratory volume (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) being 67%, 77%, and 67% of their predicted values. There was evidence of a significant reversible obstructive component in that FEV1 or PEFR or both increased by 15% or more in nine of the 23 patients after inhalation of fenoterol, the mean increases in FEV1, FVC, and PEFR for the whole group being 9.5%, 11%, and 16.9%. These results indicate that while bronchiectasis provokes a hyperimmune response it differs from cystic fibrosis in that there is no significant increase in the prevalence of atopy. The finding of reversible airways obstruction, however, suggests that bronchodilators may be useful adjuncts to treatment.

Adolescent↗
PubMed1983

Significance of elevated IgA antibody levels in neonates with gastrointestinal conditions.

Four groups of patients, 21 neonates with gastrointestinal anomalies, 8 with necrotizing enterocolitis, 5 with low anorectal anomalies and 15 with spina bifida were studied for the development of IgA and IgA subclass immunoglobulin levels. A highly significant increase in IgA levels (p less than 0.001) was seen in neonates with gastrointestinal anomalies and necrotizing enterocolitis while patients with low anorectal anomalies and spina bifida had normal or undetectable IgA levels. Estimation of IgA sub-class distribution in neonates with raised total serum IgA did not demonstrate any striking correlation between either IgA1 or IgA2 sub-classes and the clinical conditions but rather they reflected the level of total IgA. The levels if IgA, correlated closely with those of total IgA (r = 0.93) in all patients implying that in these patients total serum IgA is composed principally of IgA1 immunoglobulin.

Digestive System Abnormalities↗
PubMed1981

IgA-antibody responses in the neonate following gastrointestinal surgery.

IgA-antibody responses relative to other immunoglobulin classes were serially studied in 14 neonates undergoing gastrointestinal surgery and in a comparative group of 10 neonates undergoing surgery for neural tube defects. While IgM levels were raised postoperatively in gastrointestinal surgery patients as well in patients with neural tube defects the level of serum IgA following surgery was significantly higher in gastrointestinal patients (p less than 0.001) compared to neonates with neural tube defects. A close correlation between time of operation and an increase in IgA levels was observed. Changes in IgA antibody levels were independent of alteration in IgM and IgG levels.

Antibody Formation↗